tbuckley/cabot-search huggingface dataset:
Myeloid cell–derived proteases produce a proinflammatory form of IL-37 that signals via IL-36 receptor engagement
Authors: Graeme P. Sullivan, Pavel Davidovich, Natalia Muñoz-Wolf, Ross W. Ward, Yasmina E. Hernandez Santana, Danielle M. Clancy, Aoife Gorman, Zaneta Najda, Boris Turk, Patrick T. Walsh, Ed C. Lavelle, Seamus J. Martin
Journal: Science Immunology (2022)

Interleukin-1 (IL-1) family cytokines are key barrier cytokines that are typically expressed as inactive, or partially active, precursors that require proteolysis within their amino termini for activation. IL-37 is an enigmatic member of the IL-1 family that has been proposed to be activated by caspase-1 and to exert anti-inflammatory activity through engagement of the IL-18R and SIGIRR. However, here we show that the longest IL-37 isoform, IL-37b, exhibits robust proinflammatory activity upon amino-terminal proteolysis by neutrophil elastase or cathepsin S. In sharp contrast, caspase-1 failed to process or activate IL-37 at concentrations that robustly activated its canonical substrate, IL-1β. IL-37 and IL-36 exhibit high structural homology, and, consistent with this, a K53-truncated form of IL-37, mimicking the cathepsin S–processed form of this cytokine, was found to exert its proinflammatory effects via IL-36 receptor engagement and produced an inflammatory signature practically identical to IL-36. Administration of K53-truncated IL-37b intraperitoneally into wild-type mice also elicited an inflammatory response that was attenuated in IL-36R −/− animals. These data demonstrate that, in common with other IL-1 family members, mature IL-37 can also elicit proinflammatory effects upon processing by specific proteases.
Drug Self‐Delivery Systems: Molecule Design, Construction Strategy, and Biological Application
Authors: Chengfei Liu, Caiping Liu, Yang Bai, Jingxia Wang, Wei Tian
Journal: Advanced Healthcare Materials (2022)

Abstract Drug self‐delivery systems (DSDSs) offer new ways to create novel drug delivery systems (DDSs). In typical DSDSs, therapeutic reagents are not considered passive cargos but active delivery agents of actionable targets. As an advanced drug delivery strategy, DSDSs with positive cooperativity of both free drugs and nanocarriers exhibit the clear merits of unprecedented drug‐loading capacity, minimized systemic toxicity, and flexible preparation of nanoscale deliverables for passive targeted therapy. This review highlights the recent advances and future trends in DSDSs on the basis of two differently constructed structures: covalent and noncovalent bond‐based DSDSs. Specifically, various chemical and architectural designs, fabrication strategies, and responsive and functional features are comprehensively discussed for these two types of DSDSs. In addition, additional comments on the current development status of DSDSs and the potential applications of their molecular designs are presented in the corresponding discussion. Finally, the promising potential of DSDSs in biological applications is revealed and the relationship between preliminary molecular design of DSDSs and therapeutic effects of subsequent DSDSs biological applications is clarified.
Further Characterizing Cardiomyopathy Mortality in Young Adults to Elucidate Health Disparities
Authors: Samshita Yalamanchili, Jeffrey A. Shih, Lara C. Kovell
Journal: JAMA Cardiology (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Cardiology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Cardiology journal
NHS faces significant pressure as flu and covid cases rise
Authors: Elisabeth Mahase
Journal: BMJ (2022)

NHS faces significant pressure as flu and covid cases rise Elisabeth MahaseThe NHS received one of the highest weekly numbers of 111 calls last week as demand on the service rocketed because of covid-19, norovirus, and group A streptococcal infections.NHS England reported that NHS 111 received over 700 000 calls in the past week alone (5 to 11 December), a 60% increase on the previous week (rising from 440 047 to 706 129).This is the highest number on record, excluding two weeks at the beginning of the covid-19 pandemic (March 2020).At the same time, the number of people testing positive for covid-19 in England increased by 17% to 27 830 in the seven days up to and including 10 December. 1 Hospital admissions for covid-19 also rose by 28% to 5250 in the seven days up to and including 12 December. 2Urgent and emergency care daily situation reports 2022-23.NHS England.
Late-Breaking Science Abstracts and Featured Science Abstracts From the American Heart Association's Scientific Sessions 2022 and Late-Breaking Abstracts in Resuscitation Science From the Resuscitation Science Symposium 2022
Authors: Robert Mentz, Kevin Anstrom, Eric Eisenstein, Shelly Sapp, Stephen Greene, Shelby Morgan, Vandana Sachdev, Fassil Ketema, Dong-Yun Kim, Patrice Desvigne-Nickens, Bertram Pitt, Eric Velazquez, Areef Ishani, William Cushman, Sarah Leatherman, Robert Lew, Pa- Tricia Woods, Peter Glassman, Addison Taylor, Cynthia Hau, Alison Klint, Ryan Ferguson, Aruna Pradhan, Paul Ridker, Julian Gillmore, Jorg Taubel, Edward Gane, Bjorn Pilebro, Michael Mai- Tland, Mark Stroh, Yuanxin Xu, Adam Boyd, Jeffrey Cehelsky, David Gut- Stein, Tina Ho, Alison Sonderfan, Liron Walsh, David Lebwohl, Marianna Fontana, Douglas Lee, Sharon Straus, Michael Farkouh, Peter Austin, Moncia Taljaard, Alice Chong, Christine Fahim, Stephanie Poon, Peter Cram, Stuart Smith, Robert Mckelvie, Liane Porepa, Michael Hartleib, Peter Mitoff, Robert Iwanochko, Andrea Macdougall, Steven Shadowitz, Howard Abrams, Esam Elbarasi, Jiming Fang, Jacob Udell, Michael Schull, Su- Sanna Mak, Heather Ross, Peter Munk
Journal: Circulation (2022)

HomeCirculationVol. 146, No. 25Late-Breaking Science Abstracts and Featured Science Abstracts From the American Heart Association's Scientific Sessions 2022 and Late-Breaking Abstracts in Resuscitation Science From the Resuscitation Science Symposium 2022
Exploring functional protein covariation across single cells using nPOP
Authors: Andrew Leduc, R. Gray Huffman, Joshua Cantlon, Saad Khan, Nikolai Slavov
Journal: Genome biology (2022)

Many biological processes, such as cell division cycle and drug resistance, are reflected in protein covariation across single cells. This covariation can be quantified and interpreted by single-cell mass spectrometry with sufficiently high throughput and accuracy.
Prevention of Skin Cancers With Topical Calcipotriol and Fluorouracil in Patients With Xeroderma Pigmentosum
Authors: Juliana Kim, Stephanie A. Savory, Shadmehr Demehri, Jennifer G. Gill
Journal: JAMA Dermatology (2022)

This case report describes treatment regimens with topical calcipotriol plus fluorouracil for 2 patients with xeroderma pigmentosum.
Further Characterizing Cardiomyopathy Mortality in Young Adults to Elucidate Health Disparities—Reply
Authors: Abdul Mannan Khan Minhas, Sadiya S. Khan, Muhammad Shahzeb Khan
Journal: JAMA Cardiology (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Cardiology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Cardiology journal
Anesthesiologist Staffing Ratio and Surgical Outcome
Authors: Richard P. Dutton, Mitchell Tsai, Mark Hudson
Journal: JAMA Surgery (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
Sphingosine Kinase 2 in Stromal Fibroblasts Creates a Hospitable Tumor Microenvironment in Breast Cancer
Authors: Cynthia Weigel, Melissa A. Maczis, Elisa N.D. Palladino, Christopher D. Green, Michael Maceyka, Chunqing Guo, Xiang-Yang Wang, Mikhail G. Dozmorov, Sheldon Milstien, Sarah Spiegel
Journal: Cancer Research (2022)

Abstract Reciprocal interactions between breast cancer cells and the tumor microenvironment (TME) are important for cancer progression and metastasis. We report here that the deletion or inhibition of sphingosine kinase 2 (SphK2), which produces sphingosine-1-phosphate (S1P), markedly suppresses syngeneic breast tumor growth and lung metastasis in mice by creating a hostile microenvironment for tumor growth and invasion. SphK2 deficiency decreased S1P and concomitantly increased ceramides, including C16-ceramide, in stromal fibroblasts. Ceramide accumulation suppressed activation of cancer-associated fibroblasts (CAF) by upregulating stromal p53, which restrained production of tumor-promoting factors to reprogram the TME and to restrict breast cancer establishment. Ablation of p53 in SphK2-deficient fibroblasts reversed these effects, enabled CAF activation and promoted tumor growth and invasion. These data uncovered a novel role of SphK2 in regulating non–cell-autonomous functions of p53 in stromal fibroblasts and their transition to tumor-promoting CAFs, paving the way for the development of a strategy to target the TME and to enhance therapeutic efficacy. Significance: Sphingosine kinase 2 (SphK2) facilitates the activation of stromal fibroblasts to tumor-promoting cancer-associated fibroblasts by suppressing host p53 activity, revealing SphK2 as a potential target to reprogram the TME.
Inhibition of CD39 unleashes macrophage antibody-dependent cellular phagocytosis against B-cell lymphoma
Authors: Mika Casey, Kane Segawa, Soi Cheng Law, Muhamamed Bilal Sabdia, Bianca Nowlan, Basit Salik, Carol Lee, Clay Winterford, Sally Pearson, Jason Madore, William C. Dougall, Maher K. Gandhi, Kyohei Nakamura
Journal: Leukemia (2022)
Single-cell transcriptomics for the assessment of cardiac disease
Authors: Antonio M. A. Miranda, Vaibhao Janbandhu, Henrike Maatz, Kazumasa Kanemaru, James Cranley, Sarah A. Teichmann, Norbert Hübner, Michael D. Schneider, Richard P. Harvey, Michela Noseda
Journal: Nature Reviews Cardiology (2022)
Brd4 proteolysis-targeting chimera nanoparticles sensitized colorectal cancer chemotherapy
Authors: Yihong He, Yan Ju, Yuzhu Hu, Bilan Wang, Siyao Che, Yue Jian, Weiling Zhuo, Xianghui Fu, Yongzhong Cheng, Songping Zheng, Ning Huang, Zhiyong Qian, Jiagang Liu, Peizhi Zhou, Xiang Gao
Journal: Journal of Controlled Release (2023)
An Examination of Whether Diabetes Control and Treatments Are Associated With Change in Frailty Index Across 8 Years: An Ancillary Exploratory Study From the Action for Health in Diabetes (Look AHEAD) Trial
Authors: Felicia R. Simpson, Jamie N. Justice, Scott J. Pilla, Stephen B. Kritchevsky, Edward J. Boyko, Medha N. Munshi, Chloe K. Ferris, Mark A. Espeland
Journal: Diabetes Care (2022)

OBJECTIVE The aim of this study was to describe cross-sectional and longitudinal associations between glycated hemoglobin (HbA1c) levels and strategies to control type 2 diabetes with baseline levels and 8-year changes in a deficit accumulation frailty index (FI), a commonly used marker of biological aging. RESEARCH DESIGN AND METHODS We conducted exploratory analyses from 4,169 participants, aged 45–76 years, who were followed in the Action for Health in Diabetes (Look AHEAD) randomized controlled clinical trial, pooling data across intervention groups. We related baseline and 8-year levels of HbA1c with FI scores using analyses of variance and covariance. Associations between 8-year changes in FI and the use of diabetes medication classes and weight changes were assessed with control for HbA1c levels. Inverse probability weighting was used to assess bias associated with differential follow-up. RESULTS Baseline and average HbA1c levels over time of &amp;lt;7%, as compared with ≥8%, were associated with less increase in FI scores over 8 years (both P ≤ 0.002). After adjustment for HbA1c, use of metformin and weight loss &amp;gt;5% were independently associated with slower increases in frailty. CONCLUSIONS Lower HbA1c levels among individuals with diabetes are associated with slower biological aging as captured by a deficit accumulation FI. Strategies to control diabetes through weight loss or metformin use may also slow aging.
Can artificial intelligence pass the Fellowship of the Royal College of Radiologists examination? Multi-reader diagnostic accuracy study
Authors: Susan Cheng Shelmerdine, Helena Martin, Kapil Shirodkar, Sameer Shamshuddin, Jonathan Richard Weir-McCall
Journal: BMJ (2022)

To determine whether an artificial intelligence candidate could pass the rapid (radiographic) reporting component of the Fellowship of the Royal College of Radiologists (FRCR) examination. Prospective multi-reader diagnostic accuracy study. United Kingdom. One artificial intelligence candidate (Smarturgences, Milvue) and 26 radiologists who had passed the FRCR examination in the preceding 12 months. Accuracy and pass rate of the artificial intelligence compared with radiologists across 10 mock FRCR rapid reporting examinations (each examination containing 30 radiographs, requiring 90% accuracy rate to pass). When non-interpretable images were excluded from the analysis, the artificial intelligence candidate achieved an average overall accuracy of 79.5% (95% confidence interval 74.1% to 84.3%) and passed two of 10 mock FRCR examinations. The average radiologist achieved an average accuracy of 84.8% (76.1-91.9%) and passed four of 10 mock examinations. The sensitivity for the artificial intelligence was 83.6% (95% confidence interval 76.2% to 89.4%) and the specificity was 75.2% (66.7% to 82.5%), compared with summary estimates across all radiologists of 84.1% (81.0% to 87.0%) and 87.3% (85.0% to 89.3%). Across 148/300 radiographs that were correctly interpreted by >90% of radiologists, the artificial intelligence candidate was incorrect in 14/148 (9%). In 20/300 radiographs that most (>50%) radiologists interpreted incorrectly, the artificial intelligence candidate was correct in 10/20 (50%). Most imaging pitfalls related to interpretation of musculoskeletal rather than chest radiographs. When special dispensation for the artificial intelligence candidate was provided (that is, exclusion of non-interpretable images), the artificial intelligence candidate was able to pass two of 10 mock examinations. Potential exists for the artificial intelligence candidate to improve its radiographic interpretation skills by focusing on musculoskeletal cases and learning to interpret radiographs of the axial skeleton and abdomen that are currently considered "non-interpretable."
Mitochondrial augmentation of hematopoietic stem cells in children with single large-scale mitochondrial DNA deletion syndromes
Authors: Elad Jacoby, Omer Bar-Yosef, Noah Gruber, Einat Lahav, Nira Varda-Bloom, Yoav Bolkier, Diana Bar, Moriya Ben-Yakir Blumkin, Sharon Barak, Etzyona Eisenstein, Jaana Ahonniska-Assa, Tamar Silberg, Tal Krasovsky, Orly Bar, Neta Erez, Bella Bielorai, Hana Golan, Benjamin Dekel, Michal J. Besser, Gat Pozner, Hanan Khoury, Alan Jacobs, John Campbell, Eli Herskovitz, Noa Sher, Natalie Yivgi-Ohana, Yair Anikster, Amos Toren
Journal: Science Translational Medicine (2022)

Patients with single large-scale mitochondrial DNA (mtDNA) deletion syndromes (SLSMDs) usually present with multisystemic disease, either as Pearson syndrome in early childhood or as Kearns-Sayre syndrome later in life. No disease-modifying therapies exist for SLSMDs. We have developed a method to enrich hematopoietic cells with exogenous mitochondria, and we treated six patients with SLSMDs through a compassionate use program. Autologous CD34 + hematopoietic cells were augmented with maternally derived healthy mitochondria, a technology termed mitochondrial augmentation therapy (MAT). All patients had substantial multisystemic disease involvement at baseline, including neurologic, endocrine, or renal impairment. We first assessed safety, finding that the procedure was well tolerated and that all study-related severe adverse events were either leukapheresis-related or related to the baseline disorder. After MAT, heteroplasmy decreased in the peripheral blood in four of the six patients. An increase in mtDNA content of peripheral blood cells was measured in all six patients 6 to 12 months after MAT as compared baseline. We noted some clinical improvement in aerobic function, measured in patients 2 and 3 by sit-to-stand or 6-min walk testing, and an increase in the body weight of five of the six patients suffering from very low body weight before treatment. Quality-of-life measurements as per caregiver assessment and physical examination showed improvement in some parameters. Together, this work lays the ground for clinical trials of MAT for the treatment of patients with mtDNA disorders.
Methotrexate plus ustekinumab versus ustekinumab monotherapy in patients with active psoriatic arthritis (MUST): a randomised, multicentre, placebo-controlled, phase 3b, non-inferiority trial
Authors: Michaela Koehm, Tanja Rossmanith, Ann C Foldenauer, Eva Herrmann, Jan Brandt-Jürgens, Gerd R Burmester, Herbert Kellner, Uta Kiltz, David M Kofler, Jürgen Rech, Sorwe Mojtahed-Poor, Christin Jonetzko, Harald Burkhardt, Frank Behrens
Journal: The Lancet Rheumatology (2022)
Single-cell analysis reveals the chemotherapy-induced cellular reprogramming and novel therapeutic targets in relapsed/refractory acute myeloid leukemia
Authors: Kening Li, Yuxin Du, Yun Cai, Wenjie Liu, Yan Lv, Bin Huang, Lishen Zhang, Zhi Wang, Ping Liu, Qian Sun, Ning Li, Mengyan Zhu, Bakwatanisa Bosco, Liangyu Li, Wei Wu, Lingxiang Wu, Jianyong Li, Qianghu Wang, Ming Hong, Sixuan Qian
Journal: Leukemia (2022)

Abstract Chemoresistance and relapse are the leading cause of AML-related deaths. Utilizing single-cell RNA sequencing (scRNA-seq), we dissected the cellular states of bone marrow samples from primary refractory or short-term relapsed AML patients and defined the transcriptional intratumoral heterogeneity. We found that compared to proliferating stem/progenitor-like cells (PSPs), a subpopulation of quiescent stem-like cells (QSCs) were involved in the chemoresistance and poor outcomes of AML. By performing longitudinal scRNA-seq analyses, we demonstrated that PSPs were reprogrammed to obtain a QSC-like expression pattern during chemotherapy in refractory AML patients, characterized by the upregulation of CD52 and LGALS1 expression. Flow cytometric analysis further confirmed that the preexisting CD99 + CD49d + CD52 + Galectin-1 + (QSCs) cells at diagnosis were associated with chemoresistance, and these cells were further enriched in the residual AML cells of refractory patients. Interaction of CD52-SIGLEC10 between QSCs and monocytes may contribute to immune evading and poor outcomes. Furthermore, we identified that LGALS1 was a promising target for chemoresistant AML, and LGALS1 inhibitor could help eliminate QSCs and enhance the chemotherapy in patient-derived primary AML cells, cell lines, and AML xenograft models. Our results will facilitate a better understanding of the AML chemoresistance mechanism and the development of novel therapeutic strategies for relapsed/refractory AML patients.
Corrigendum to “Adrenocortical carcinomas and malignant phaeochromocytomas: ESMO-EURACAN Clinical Practice Guidelines for diagnosis, treatment and follow-up”
Authors: M. Fassnacht, G. Assie, E. Baudin, G. Eisenhofer, C. de la Fouchardiere, H.R. Haak, R. de Krijger, F. Porpiglia, M. Terzolo, A. Berruti
Journal: Annals of Oncology (2022)
Corrigendum to “Tucatinib versus placebo added to trastuzumab and capecitabine for patients with pretreated HER2D metastatic breast cancer with and without brain metastases (HER2CLIMB): final overall survival analysis”
Authors: G. Curigliano, V. Mueller, V. Borges, E. Hamilton, S. Hurvitz, S. Loi, R. Murthy, A. Okines, E. Paplomata, D. Cameron, L.A. Carey, K. Gelmon, G.N. Hortobagyi, I. Krop, S. Loibl, M. Pegram, D. Slamon, J. Ramos, W. Feng, E. Winer
Journal: Annals of Oncology (2022)
Recurrent germline variant in ATM associated with familial myeloproliferative neoplasms
Authors: Evan M. Braunstein, Eddie Imada, Sergiu Pasca, Shiyu Wang, Hang Chen, Camille Alba, Dan N. Hupalo, Matthew Wilkerson, Clifton L. Dalgard, Jack Ghannam, Yujia Liu, Luigi Marchionni, Alison Moliterno, Christopher S. Hourigan, Lukasz P. Gondek
Journal: Leukemia (2022)